The Vietnam Chloroquine Treatment on COVID-19

COVID-19 Clinical Trial

— VICO  

Official title:

A Multi Center Randomized Open Label Trial on the Safety and Efficacy of Chloroquine for the Treatment of Hospitalized Adults With Laboratory Confirmed SARS-CoV-2 Infection in Vietnam

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04328493
• Other study ID #: COVID
• Status: Completed
• Phase: Phase 2
• Start date: April 7, 2020
• Est. completion date: September 10, 2020

Study information

• Verified date: May 2021
• Source: Oxford University Clinical Research Unit, Vietnam
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

COVID-19 is a respiratory disease caused by a novel coronavirus (SARS-CoV-2) and causes substantial morbidity and mortality. There is currently no vaccine to prevent COVID-19 or therapeutic agent to treat COVID-19. This clinical trial is designed to evaluate potential therapeutics for the treatment of hospitalized COVID-19.

We hypothesis that chloroquine slows viral replication in patients with COVID-19, attenuating the infection, and resulting in more rapid declines in viral load in throat swabs. This viral attenuation should be associated with improved patient outcomes. Given the enormous experience of its use in malaria chemoprophylaxis, excellent safety and tolerability profile, and its very low cost, if proved effective then chloroquine would be a readily deployable and affordable treatment for patients with COVID-19.

The study is funded and leaded by The Ministry of Health, Vietnam.

Description:

The study will start with a 10-patient prospective observational pilot study. All these patients will be subject to the same entry and exclusion criteria for the randomized trial, and undergo the same procedures. They will all receive chloroquine at the doses used in the trial (see sections below); they will not be randomized. The purpose of the pilot is to develop the study procedures for the randomized controlled trial, including the safe monitoring of patients, to refine the CRF, and to acquire some preliminary data on the safety of chloroquine in those with COVID-19.

Once the pilot study has been completed, and the data reviewed by the TSC and DMC, and the MOH ethics committee, we will then proceed to the trial. We will aim for minimum delay between completing the pilot study and starting the randomized trial.

The main study is an open label, randomised, controlled trial that will be conducted in 240 in-patients in Ho Chi Minh City. Viet Nam.

Patients will have daily assessment as per standard of care while in-patients by the hospital staff. While in-patients the study will collect the following data: peripheral oxygen saturation (pulse oximeter), respiratory rate, and FiO2. These will be recorded between 2 and 4 times per day depending on the practice of the treating site. Where recording is twice daily, one record will be made from the time period of 00:00 until 12:00, and the second recording between 12:01 and 23:59. Where the parameters are recorded four times/day they will be recorded in each of the time periods 00:00 - 06:00, 06:01 - 12:00, 12:01 - 18:00 and 18:01

• 23:59. Vitals recorded will include: FiO2, SpO2, Temp, RR HR BP. The use of ventilator or other assisted breathing device will be recorded each day.

Patients will have clinical assessment recorded as per the study schedule.

The decision to discharge patients will be at the discretion of the attending physician and depend upon the clinical status of the patient. According to current standard of care recovery and hospital discharge is dependent upon the patient having had 2 daily consecutive negative PCR throat/nose swabs. Following discharge patients will be seen on days 14, 28, 42 and 56 post-randomization.

In a subset of patients admitted to HTD we will look for ECG changes, using real-time monitoring.

Patients will have up to 1 hour ECG continuous recordings daily. The ECG recording will be downloaded from standard monitor (GE Careview) and stored electronically. ECG changes (including QT interval) will then be analyzed by machine learning.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: September 10, 2020
• Est. primary completion date: September 10, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

1. Laboratory-confirmed SARS-CoV-2 infection as determined by PCR, or other commercial or public health assay in any specimen < 48 hours prior to randomization, and requiring hospital admission in the opinion of the attending physician.

2. Provides written informed consent prior to initiation of any study procedures (or legally authorized representative).

3. Understands and agrees to comply with planned study procedures.

4. Agrees to the collection of OP swabs and venous blood per protocol.

5. Male or female adult =18 years of age at time of enrollment.

Related Conditions & MeSH terms

• COVID-19
• Infection
• SARS-CoV-2 Infection

Intervention

Drug:
• Chloroquine phosphate
Each chloroquine tablet contains 250mg chloroquine phosphate (or 150mg chloroquine base). Chloroquine treatment for patient is weight-based dosing. Chloroquine will be administered orally, as tablets. For unconscious patients chloroquine can be crushed and administered as a suspension via a nasogastric tube. The total duration of treatment with Chloroquine will be 10 days

Locations

Country	Name	City	State
Vietnam	National Hospital for Tropical Diseases	Hanoi
Vietnam	Can Gio COVID Hospital	Ho Chi Minh City
Vietnam	Cho Ray Hospital	Ho Chi Minh City
Vietnam	Cu Chi COVID Hospital	Ho Chi Minh City
Vietnam	Hospital for Tropical Diseases	Ho Chi Minh City

Sponsors (8)

Lead Sponsor	Collaborator
Oxford University Clinical Research Unit, Vietnam	Can Gio COVID Hospital, Vietnam, Cho Ray Hospital, Cu Chi COVID Hospital, Vietnam, Department of Health, Ho Chi Minh city, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam, Ministry of Health, Vietnam, National Hospital for Tropical Diseases, Hanoi, Vietnam

Country where clinical trial is conducted

Vietnam, 

References & Publications (18)

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Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends. 2020 Mar 16;14(1):72-73. doi: 10.5582/bst.2020.01047. Epub 2020 Feb 19. — View Citation

Gordon CJ, Tchesnokov EP, Feng JY, Porter DP, Götte M. The antiviral compound remdesivir potently inhibits RNA-dependent RNA polymerase from Middle East respiratory syndrome coronavirus. J Biol Chem. 2020 Apr 10;295(15):4773-4779. doi: 10.1074/jbc.AC120.013056. Epub 2020 Feb 24. — View Citation

Jorge A, Ung C, Young LH, Melles RB, Choi HK. Hydroxychloroquine retinopathy - implications of research advances for rheumatology care. Nat Rev Rheumatol. 2018 Dec;14(12):693-703. doi: 10.1038/s41584-018-0111-8. Review. — View Citation

Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, Ren R, Leung KSM, Lau EHY, Wong JY, Xing X, Xiang N, Wu Y, Li C, Chen Q, Li D, Liu T, Zhao J, Liu M, Tu W, Chen C, Jin L, Yang R, Wang Q, Zhou S, Wang R, Liu H, Luo Y, Liu Y, Shao G, Li H, Tao Z, Yang Y, Deng Z, Liu B, Ma Z, Zhang Y, Shi G, Lam TTY, Wu JT, Gao GF, Cowling BJ, Yang B, Leung GM, Feng Z. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. N Engl J Med. 2020 Mar 26;382(13):1199-1207. doi: 10.1056/NEJMoa2001316. Epub 2020 Jan 29. — View Citation

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Villegas L, McGready R, Htway M, Paw MK, Pimanpanarak M, Arunjerdja R, Viladpai-Nguen SJ, Greenwood B, White NJ, Nosten F. Chloroquine prophylaxis against vivax malaria in pregnancy: a randomized, double-blind, placebo-controlled trial. Trop Med Int Health. 2007 Feb;12(2):209-18. — View Citation

Vincent MJ, Bergeron E, Benjannet S, Erickson BR, Rollin PE, Ksiazek TG, Seidah NG, Nichol ST. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J. 2005 Aug 22;2:69. — View Citation

Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z, Hu Z, Zhong W, Xiao G. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020 Mar;30(3):269-271. doi: 10.1038/s41422-020-0282-0. Epub 2020 Feb 4. — View Citation

White NJ, Miller KD, Churchill FC, Berry C, Brown J, Williams SB, Greenwood BM. Chloroquine treatment of severe malaria in children. Pharmacokinetics, toxicity, and new dosage recommendations. N Engl J Med. 1988 Dec 8;319(23):1493-500. — View Citation

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* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Viral clearance time	Viral presence will be determined using RT-PCR to detect SARS-CoV-19 RNA. Throat/nose swabs for viral RNA will be taken daily while in hospital until there have at least 2 consecutive negative results . Virus will be defined as cleared when the patient has had =2 consecutive negative PCR tests. The time to viral clearance will be defined as the time following randomization to the first of the negative throat/nose swabs.	Up to 56 days post randomization
Secondary	Length of hospital stay	The time since randomization to discharge between study groups	Up to 56 days post randomization
Secondary	Ventilator free days	The number of ventilator free days over the first 28 days of treatment	first 28 days
Secondary	Oxygen free days	The number of oxygen free days over the first 28 days of treatment	first 28 days
Secondary	Time to death	The time to (all-cause) death following over the first 7, 10, 14, 28 and 56 days since randomization	first 7, 10, 14, 28 and 56 days since randomization
Secondary	Adverse events	The rates of serious adverse events, rates of grade 3 or 4 adverse events	Over the first 28 days (due to the prolonged half-life of Chloroquine)
Secondary	fever clearance time	Time since randomization to the first defervescence day	Up to 56 days post randomization
Secondary	Ordinal outcome scale	WHO Ordinal outcome scale for COVID-19	Up to 56 days post randomization
Secondary	Development of ARDS	Development of ARDS defined by the Kigali criteria	Up to 56 days post randomization

External Links

•   COVID-19 Coronavirus Pandemic updates
•   in press
•   World Health Organization Model List of Essential Medicines